It is estimated that more than 13 million Americans are afflicted with clinically significant coronary artery disease (CAD) (American Heart Association 2004) and the care of these patients costs greater than $133 billion annually. Of those afflicted, 10% are less than 54 years old. Although a minority of the patient base, this group provides a valuable source for the investigation of the genetics underlying cardiac disease risk, because family history is known to be a robust predictor of cardiovascular disease, even after adjustment for known risk factors, which may be shared within families (Shea et al. 1984). Furthermore, these diseases inflict a high economic impact on this group of patients with early onset CAD. The identification of novel markers correlated with CAD is important in order to understand the pathophysiological mechanisms of this disease state and develop effective prevention and treatment regimens.
Cardiovascular disease is the leading killer in America today. Over 50 million Americans have heart and cardiovascular related problems. By the time that cardiovascular heart problems are usually detected, the disease is usually quite advanced, having progressed for decades, and often too advanced to allow successful prevention of major permanent disability.
Circulatory disease is caused by the normal flow of blood through the body being restricted or blocked as a result of arterial plaque. This may cause damage to the heart, brain, kidneys or other organs and tissues. Plaque build-up is a slow and progressive progress that is dependent on our environmental and genetic environment.
Cardiovascular disease refers to all disease, which involves the heart and/or blood vessels, arteries, and occasionally veins. These problems are most commonly due to consequences of arterial disease, atherosclerosis, atheroma, but also can be related to infection, valvular and clotting problems.
In humans, β1-adrenergic receptors (β1-ARs) are polymorphic at amino acid residue 389 (Arg/Gly). Mialet-Perez et al. (2003) Nat Med. 9:1260-1262, catecholamines stimulate cardiac contractility through reported that the human Arg389 variant predisposes to heart failure by instigating hyperactive signaling programs leading to depressed receptor coupling and ventricular dysfunction, and influences the therapeutic response to β-receptor blockade.
The present invention overcomes previous shortcomings in the art by providing methods and compositions for correlating genetic markers in a subject with various aspects of cardiovascular disease and its treatment.